Several nerve guidance conduits (NGCs) and nerve protectant wraps are approved by the US Food and Drug Administration (FDA) for clinical use in peripheral nerve repair. These devices cover a wide range of natural and synthetic materials, which may or may not be resorbable. This review consolidates the data pertaining to all FDA approved materials into a single reference, which emphasizes material composition alongside pre-clinical and clinical safety and efficacy (where possible). This article also summarizes the key advantages and limitations for each material as noted in the literature (with respect to the indication considered). In this context, this review provides a comprehensive reference for clinicians which may facilitate optimal material/device selection for peripheral nerve repair. For materials scientists, this review highlights predicate devices and evaluation methodologies, offering an insight into current deficiencies associated with state-of-the-art materials and may help direct new technology developments and evaluation methodologies thereof.

FDA approved guidance conduits and wraps for peripheral nerve injury: A review of materials and efficacy

Schwann cells develop from the neural crest in a well-defined sequence of events. This involves the formation of the Schwann cell precursor and immature Schwann cells, followed by the generation of the myelin and nonmyelin (Remak) cells of mature nerves. This review describes the signals that control the embryonic phase of this process and the organogenesis of peripheral nerves. We also discuss the phenotypic plasticity retained by mature Schwann cells, and explain why this unusual feature is central to the striking regenerative potential of the peripheral nervous system (PNS).

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Schwann Cells: Development and Role in Nerve Repair

Construction of tissue engineered nerve grafts and their application in peripheral nerve regeneration

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Neural tissue engineering options for peripheral nerve regeneration

Repairing injured peripheral nerves: Bridging the gap

Nerve repair is usually accomplished by direct suture when the two stumps can be approximated without tension. In the presence of a nerve defect, the placement of an autologous nerve graft is the current gold standard for nerve restoration. However, over the last 20 years, an increasing number of research articles reported on the use of non-nervous tubes (tubulization) for repairing nerve defects. The clinical employment of tubes (both biological and synthetic) as an alternative to autogenous nerve grafts is mainly justified by the limited availability of donor tissue for nerve autografts and the related morbidity. In addition, tubulization was proposed as an alternative to direct nerve sutures in order to create optimal conditions for nerve regeneration over the short empty space intentionally left between two nerve stumps. This paper outlines recent important advances in this field. Different tubulization techniques proposed so far are described, focusing in particular on studies that reported on the employment of tubes with patients. Our personal clinical experience on tubulization repair of sensory nerve lesions (digital nerves), using both biological and synthetic tubes, is presented, and the clinical results are compared. In our case series, both types of tubes led to good clinical results. Finally, we speculate about the prospects in the clinical application of tubulization for peripheral nerve repair.

Nerve repair by means of tubulization: literature review and personal clinical experience comparing biological and synthetic conduits for sensory nerve repair.

The use of vein or muscle grafts to bridge nerve defects longer than 1-1.5 cm gives poor results. Veins collapse and in muscle grafts axons may regrow outside the graft. We used veins (to guide regeneration) filled with muscle (to avoid vein collapse). Nerve regeneration through 1 and 2 cm grafts made of vein plus muscle was compared with similarly long traditional nerve grafts, free fresh muscle grafts, and empty vein grafts. Regeneration was assessed clinically and histologically (qualitative and quantitative evaluation) in the graft and distal nerve stumps. Vein plus muscle grafts were superior to vein and fresh muscle grafts both functionally and histologically. Functional results were similar to those found in traditional nerve grafts, but axon number was superior in the veins filled with muscle. This suggests that vein filled with muscle might serve as a grafting conduit for the repair of peripheral nerve injuries and could give better results than traditional nerve grafting. © 1993 Wiley-Liss Inc.

Bridging nerve defects with combined skeletal muscle and vein conduits.

Facial nerve reconstruction for lesions with nerve gaps frequently require autologous or tubulized grafts of biological or synthetic origin. Neurotube, a bioabsorbable polyglycolic acid tube, represents a valid solution for this kind of defect in emergency and planned surgery. Seven posttraumatic lesions of terminal branches of the facial nerve were repaired by means of Neurotube from September 1999-September 2001. The nerve gap size ranged between 1-3 cm. Nerve regeneration was evaluated at 7-12 months of follow-up when muscle recovery function was examined. Muscle function was very good in 1 case, good in 4, and fair in 2 (71% positive results). No intolerance or discomfort was reported or observed. Neurotube is useful for the reconstruction of facial nerve lesions with a small nerve gap (less then 3 cm) when a direct anastomosis of the two stumps is not possible, or when the suture appears to be in tension. It is a valid alternative to autologous and biological tubulized grafts. The limits of this method are: 1) it can only be used with gaps of less than 3 cm; 2) it is quite costly; 3) there are reports of possible intolerance; and 4) it is not suitable for lesions of the proximal part of the facial nerve.

Neurotube for facial nerve repair.

The morphological features of regeneration in long-distance (3 cm) muscle-vein-combined grafts were experimentally investigated in the rat sciatic nerve by means of light and electron microscopy. In the early phases of regeneration (14 days after surgery), many regenerating nerve fibers were detected along the muscle-vein-combined graft. Six months after surgery, quantitative morphometrical analysis of myelinated nerve fibers showed that both the total number and density of myelinated nerve fibers were significantly greater in regenerated nerves than in control nerves. The contrary appeared true for the mean fiber size, with fiber size significantly smaller in regenerated nerves. Ultrastructural observations allowed the description of some peculiar aspects of the relationship between muscle fibers, nerve fibers, and Schwann cells in both early and late phases of regeneration.

Nerve repair by means of vein filled with muscle grafts. II. Morphological analysis of regeneration.

The need for reconstruction of lower limb amputations is increasing, due to high-energy trauma in road accidents and work-related injuries. The indication for lower limb replantation is still controversial. Compared with upper limb replantations, indications are more select due to the frequent complications in lower limb salvage procedures, such as severe general complications or local complications such as necrosis, infections, nonunions, the need for secondary lengthening, or other reconstructive procedures. The satisfactory results given by artificial prosthesis, such as quicker recovery time and fewer secondary procedures, also contribute to the higher degree of selection for lower limb replantation candidates. Since 1993, we have replanted 14 amputations of the lower limb in 12 patients, including 2 bilateral cases. Although survival of the replanted segment was obtained in all patients, 5 cases were subsequently amputated for severe secondary complications. Of the remaining 9 cases, evaluated by means of Chen criteria, 7 had good results (3 Chen I and 4 Chen II), 1 sufficient (Chen III), and 1 poor (Chen IV). The best results were obtained in young patients. Our experience led us to examine the necessity for careful, objective patient selection. We developed a score evaluation system by modifying the international classifying method for severe limb traumas (mangled extremity severity score, or MESS system). This relatively simple system, based on the retrospective study of our cases, considers several parameters (patient's age, general conditions, level and type of lesion, time of injury, and associated lesions), giving each one a score. The total score gives the indication for replantation, predicts the functional outcome, and facilitates decision-making.

Bruno Battiston

Papers

Nerve repair by means of tubulization: literature review and personal clinical experience comparing biological and synthetic conduits for sensory nerve repair.

Bridging nerve defects with combined skeletal muscle and vein conduits.

Neurotube for facial nerve repair.

Nerve repair by means of vein filled with muscle grafts. II. Morphological analysis of regeneration.

Lower limb replantations: indications and a new scoring system.